POSSIBLE ROLE OF CYTOSOLIC FREE CALCIUM CONCENTRATIONS IN MEDIATING INSULIN RESISTANCE OF OBESITY AND HYPERINSULINEMIA
POSSIBLE ROLE OF CYTOSOLIC FREE CALCIUM CONCENTRATIONS IN MEDIATING INSULIN RESISTANCE OF OBESITY AND HYPERINSULINEMIA
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DOI：
10.1172/jci113801
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发表时间：
1988-12-01
影响因子：
15.9
通讯作者：
SHERMAN, NA
中科院分区：
文献类型：
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作者：
DRAZNIN, B;SUSSMAN, KE;SHERMAN, NA
研究了胰岛素和格列本脲刺激的6名肥胖妇女（139 ± 100 μ g/kg）臀脂肪细胞胞浆游离钙浓度（[Ca 2 +] i）的变化。3%理想体重）和六个健康的、正常体重的年龄和性别匹配的对照。在空腹过夜后进行活检，并在胰岛素输注（40 mU/m2/min）（正葡萄糖钳夹）期间进行两次（3 h和6 h）活检。在胰岛素输注前从正常受试者获得的脂肪细胞中，胰岛素（10 ng/ml）使[Ca2 +] i从146 ± 1增加。26 nM至391 ±。66 nM。用2 μ M格列本脲（329 ± 0.01）诱发类似的增加。41 nM）。胰岛素输注3小时后，基础[Ca2 +] i上升至234. ±. 21 nM，但对胰岛素和格列本脲的反应完全消除。胰岛素和葡萄糖输注降低了体外胰岛素刺激的2-脱氧葡萄糖摄取（输注前刺激25%，输注3小时刺激5.4%，输注6小时刺激0.85%）。在肥胖患者中，基础脂肪细胞[Ca2 +] i增加（203. ±. 14nM，P <0.05相对于正常）。[Ca2 +] i反应表明对胰岛素的抗性（230 ± 0.01）。23 nM）和格列本脲（249. ±. 19 nM）刺激。持续胰岛素输注增加基础[Ca 2 +] i（244. ±. 24 nM），并且在研究的3和6小时对胰岛素或格列本脲均无应答。将大鼠脂肪细胞与1 - 10 mM葡萄糖和10 ng/ml胰岛素预孵育24 h。2-deoxglucose摄取的测量表明这些细胞中存在胰岛素抵抗。在这些实验条件下，证明了不再对胰岛素有反应的[Ca2 +] i水平增加。预孵育培养基中的维拉帕米可防止胰岛素抵抗的发生。
Insulin- and glyburide-stimulated changes in cytosolic free calcium concentrations ([Ca2+]i) were studied in gluteal adipocytes obtained from six obese women (139 .+-. 3% ideal body wt) and six healthy, normal weight age- and sex-matched controls. Biopsies were performed after an overnight fast and twice (at 3 and 6 h) during an insulin infusion (40 mU/m2 per min) (euglycemic clamp). In adipocytes obtained from normal subjects before insulin infusion, insulin (10 ng/ml) increased [Ca2+]i from 146 .+-. 26 nM to 391 .+-. 66 nM. Similar increases were evoked by 2 .mu.M glyburide (329 .+-. 41 nM). After 3 h of insulin infusion, basal [Ca2+]i rose to 234 .+-. 21 nM, but the responses to insulin and glyburide were completely abolished. In vitro insulin-stimulated 2-deoxyglucose uptake was reduced by insulin and glucose infusion (25% stimulation before infusion, 5.4% at 3 h, and 0.85% at 6 h of infusion). In obese patients, basal adipocyte [Ca2+]i was increased (203 .+-. 14 nM, P < 0.05 vs. normals). The [Ca2+]i response demonstrated resistance to insulin (230 .+-. 23 nM) and glyburide (249 .+-. 19 nM) stimulation. Continuous insulin infusion increased basal [Ca2+]i (244 .+-. 24 nM) and there was no response to either insulin or glyburide at 3 and 6 h of study. Rat adipocytes were preincubated with 1-10 mM glucose and 10 ng/ml insulin for 24 h. Measurements of 2-deoxglucose uptake demonstrated insulin resistance in these cells. Under these experimental conditions, increased levels of [Ca2+]i that were no longer responsive to insulin were demonstrated. Verapamil in the preincubation medium prevented the development of insulin resistance.